Open AccessInhibition of Platelet‐Derived Growth Factor Receptor Signaling Regulates Oct4 and Nanog Expression, Cell Shape, and Mesenchymal Stem Cell Potency
Author(s) -
Ball Stephen G.,
Shuttleworth Adrian,
Kielty Cay M.
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1015
Subject(s) - homeobox protein nanog , biology , microbiology and biotechnology , mesenchymal stem cell , receptor tyrosine kinase , platelet derived growth factor receptor , stem cell , growth factor receptor , signal transduction , rex1 , cellular differentiation , cancer research , growth factor , receptor , embryonic stem cell , adult stem cell , induced pluripotent stem cell , biochemistry , gene
Defining the signaling mechanisms that regulate the fate of adult stem cells is an essential step toward their use in regenerative medicine. Platelet‐derived growth factor receptor (PDGFR) signaling plays a crucial role in specifying mesenchymal stem cell (MSC) commitment to mesenchymal lineages. Based on the hypothesis that selective inhibition of signaling pathways involved in differentiation may increase stem cell potency, we examined the role of PDGFR signaling in controlling the fate of human MSCs. Using a small molecular PDGFR inhibitor that induced MSCs toward a more rounded shape, expression of Oct4 and Nanog were markedly upregulated. In these PDGFR inhibitor‐treated MSCs, Oct4 and Nanog expression and cell shape were regulated by janus kinase (JAK), MAPK kinase (MEK), and epidermal growth factor receptor (EGFR) signaling. Under defined differentiation conditions, these PDGFR‐inhibited MSCs expressed definitive endodermal, ectodermal, and mesodermal markers. We also confirmed that depletion of individual PDGF receptors upregulated expression of Oct4A and Nanog. This study identifies PDGFR signaling as a key regulator of Oct4 and Nanog expression and of MSC potency. Thus, inhibiting these specific receptor tyrosine kinases, which play essential roles in tissue formation, offers a novel approach to unlock the therapeutic capacity of MSCs. S TEM C ELLS 2012;30:548–560